Efficacy, Safety and Tolerability Study of APL-130277 for the Acute Treatment of OFF Episodes in Patients With Parkinson's Disease
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Examine the Efficacy, Safety and Tolerability of APL-130277 in Levodopa Responsive Patients With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
1 other identifier
interventional
141
2 countries
33
Brief Summary
A 12-week, prospective, multi-center, randomized, double-blind, placebo controlled, Phase 3 study in L-Dopa responsive PD patients with motor fluctuations ("OFF" episodes), designed to determine the efficacy, safety and tolerability of APL-130277.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jun 2015
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 9, 2015
CompletedFirst Posted
Study publicly available on registry
June 11, 2015
CompletedStudy Start
First participant enrolled
June 18, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 11, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 11, 2017
CompletedResults Posted
Study results publicly available
July 30, 2020
CompletedJuly 30, 2020
July 1, 2020
2.5 years
June 9, 2015
June 19, 2020
July 15, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Mean Change From Pre-Dose to 30 Minutes Post-Dose in The Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score at Maintenance Visit 4 (MV4) - Week 12
The Motor Function section (Part III) of the MDS-UPDRS was administered by the Investigator, and included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The least square mean change in the MDS-UPDRS Part III score from pre-dose to 30 minutes post-dose at MV4 is presented. A negative change from pre-dose indicates an improvement.
At t=0 (just prior to dosing) and t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).
Secondary Outcomes (9)
Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes at MV4 - Week 12: Predicted Response Rate
At t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).
Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes That Had a Duration of Effect of at Least 30 Minutes at MV4 - Week 12: Predicted Response Rate
At MV4 (Week 12 of the Maintenance Treatment Phase).
Patient Global Impression of Improvement (PGI-I): Percentage of Patients Who Improved at MV4 - Week 12
At MV4 (Week 12 of the Maintenance Treatment Phase).
Clinician Global Impression of Improvement (CGI-I): Percentage of Patients Who Improved at MV4 - Week 12
At MV4 (Week 12 of the Maintenance Treatment Phase).
Mean Change From Screening Visit to MV4 (Week 12) in MDS-UPDRS Part II: Motor Aspects of Experience of Daily Living
At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase).
- +4 more secondary outcomes
Study Arms (2)
APL-130277
EXPERIMENTALAPL-130277 sublingual thin film (10 mg, 15 mg, 20 mg, 25 mg, 30 mg and 35 mg)
Placebo
PLACEBO COMPARATORMatching placebo for APL-130277 sublingual thin film (10 mg, 15 mg, 20 mg, 25 mg, 30 mg and 35 mg)
Interventions
Use to treat up to 5 "OFF" episodes per day
Eligibility Criteria
You may qualify if:
- Male or female ≥ 18 years of age.
- Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria.
- Clinically meaningful response to L-Dopa with well-defined early morning "OFF" episodes, as determined by the Investigator.
- Receiving stable doses of L-Dopa/carbidopa (immediate or CR) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the initial Screening Visit
- No planned medication change(s) or surgical intervention anticipated during the course of study.
- Patients must experience at least one well defined "OFF" episode per day with a total daily "OFF" time duration of ≥ 2 hours during the waking day, based on patient self-assessment.
- Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
- MMSE score \> 25.
You may not qualify if:
- Atypical or secondary parkinsonism.
- Previous treatment with any of the following: a neurosurgical procedure for PD; continuous s.c. apomorphine infusion; or Duodopa/Duopa.
- Treatment with any form of s.c. apomorphine within 7 days prior to the initial Screening Visit (SV1). Patients that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
- Contraindications to APOKYN®, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of APOKYN® (notably sodium metabisulfite); Tigan® (trimethobenzamide hydrochloride; patients from US sites only); or domperidone (patients from non-US sites only).
- Participation in a clinical trial within 30 days prior to the initial Screening Visit (SV1).
- Currently taking selective 5HT3 antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents.
- Drug or alcohol dependency in the past 12 months.
- History of malignant melanoma.
- Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
- Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
- History of clinically significant hallucinations during the past 6 months.
- History of clinically significant impulse control disorder(s).
- Dementia that precludes providing informed consent or would interfere with participation in the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
University of Alabama, Birmingham
Birmingham, Alabama, 35233, United States
Muhammed Ali Parkinson and Movement Disorder CenterBarrow Neurological
Phoenix, Arizona, United States
Movement Disorders Center of Arizona
Scottsdale, Arizona, 85258, United States
Mayo Clinic Arizona
Scottsdale, Arizona, 85259, United States
The Parkinson's and Movement Disorder Institute
Fountain Valley, California, 92708, United States
UC Irvine Health Gottschalk Medical Plaza
Irvine, California, 92697, United States
Keck Medical Center at USC
Los Angeles, California, 90033, United States
The Research Center of Southern California
Oceanside, California, 92056, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Parkinsons Disease and Movement Disorders Center
Boca Raton, Florida, 33486, United States
University of Miami, Miller School of Medicine
Miami, Florida, 33136, United States
Parkinson's Disease Treatment Center of Southwest Florida
Port Charlotte, Florida, 33980, United States
USF Parkinson's Disease and Movement Disorder Center
Tampa, Florida, 33613, United States
Emory University Department of Neurology
Atlanta, Georgia, 30329, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center
Winfield, Illinois, 60190, United States
Kansas University Medical Center - Department of Neurology
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
QUEST Research Institute
Farmington Hills, Michigan, 48334, United States
Northern Michigan Neurology
Traverse City, Michigan, 49684, United States
Henry Ford Hospital
West Bloomfield, Michigan, 48322, United States
Columbia University Medical Center - Neurological Institute, Movement Disorders
New York, New York, 10032, United States
Raleigh Neurology Associates, P.A.
Raleigh, North Carolina, 27607, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati
Cincinnati, Ohio, 45219, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
The Movement Disorder Clinic of Oklahoma
Tulsa, Oklahoma, 74136, United States
Jefferson University Hospital Philadelphia
Philadelphia, Pennsylvania, 19107, United States
University of Virginia, Adult Neurology
Charlottesville, Virginia, 22903, United States
Evergreen Health
Kirkland, Washington, 98034, United States
UHN Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Related Publications (1)
Olanow CW, Factor SA, Espay AJ, Hauser RA, Shill HA, Isaacson S, Pahwa R, Leinonen M, Bhargava P, Sciarappa K, Navia B, Blum D; CTH-300 Study investigators. Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol. 2020 Feb;19(2):135-144. doi: 10.1016/S1474-4422(19)30396-5. Epub 2019 Dec 7.
PMID: 31818699DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- CNS Medical Director
- Organization
- Sunovion Pharmaceuticals Inc.
Study Officials
- STUDY DIRECTOR
CNS Medical Director
Sumitomo Pharma America, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 9, 2015
First Posted
June 11, 2015
Study Start
June 18, 2015
Primary Completion
December 11, 2017
Study Completion
December 11, 2017
Last Updated
July 30, 2020
Results First Posted
July 30, 2020
Record last verified: 2020-07